The goal of the proposed research is to elucidate the genetic mechanism controlling the antibody variability and the application of this knowledge to combat inherited and immunodeficiency diseases. Amino acid sequence determination and analyses of inherited antigenic determinants (Gm, Am, Km, Mm and idiotypic markers) will be conducted on immunoglobulins from normal individuals, as well as patients with multiple myeloma, Waldenstrom's macroglobulinemia, hypogammaglobulinemia, idiopathic cryoagglutininemia, cryoglobulinemia and various other immunodeficiency conditions. Results obtained from these studies will be analyzed in order to determine if any correlation exists between the structure of the abnormal immunoglobulins and the diseases with which they are associated. We also are attempting to use the maturation of immunoglobulin producing cells as a simple model system for the investigation of various aspects of differentiation and "regulatory" control of gene expression in other complex genetic systems in higher organisms. BIBLIOGRAPHIC REFERENCES: Wang, A.C., and Fudenberg, H.H.: Chemical studies on a monoclonal immunoglobulin from a patient with carcinoma of the colon. Immunol. Commun. 4(5): 483-497, 1975. Rajnavolgyi, E., Wang, A.C., Medgyesi, G.A. and Gergely, J.: Factors affecting chain-interactions in immunoglobulins and their significance in cold agglutinin activity. Immunochemistry 12: 663-666, 1975.